STREPTOMYCIN 389 



stroy the antibiotic. Since this drug may be inactivated by metals 

 such as copper, lead, cadmium, zinc, and to a lesser degree by nickel, 

 mercury, and uranium,^ such substances must not be present in the 

 equipment used to produce or process it. 



The methods used in purifying penicillin have not been made 

 available to the public as yet. However, according to Coghill * 

 present-day methods are but variants of those originally reported by 

 the Oxford University group of workers. These investigators puri- 

 fied penicillin by first adjusting the pH of the broth to a point between 

 2.0 and 3.0 and extracting the penicillin (which behaves like an 

 organic acid) with a solvent such as ether, chloroform, or amyl 

 acetate. Since the drug is highly unstable at this pH, this procedure 

 must be carried out at as low a temperature and in as short a period 

 of time as possible. The penicillin, now in the organic solvent, is 

 extracted with a solution of sodium bicarbonate. By repeating this 

 process, shuttling the antibiotic between solvents and buffer solutions 

 of the appropriate pH, the penicillin can be obtained in purer form. 

 Since penicillin is unstable in aqueous solutions, the preparations 

 must be frozen and dried from this state, lyophilized, in much the 

 same manner that our dried plasma is prepared. Present-day prep- 

 arations of the drug are a pale yellow to a dark brown powder con- 

 taining from 100 to 500 units per milligram. They generally are 

 mixtures of sodium salts of some of the organic acids originally 

 present in the culture medium and have a sodium penicillin content 

 of about 8 to 30 per cent. The preparations are rigorously tested 

 for strength, sterility, toxicity, and pyrogens. 



It has become apparent recently ^^ that most of the samples of 

 penicillin preparations are mixtures of at least two and sometimes 

 three distinct chemical entities. In the United States they have been 

 designated as penicillins F, G, and X, and as I, II, and III in England. 

 They often occur in widely differing proportions in various samples. 

 Schmidt, Ward, and Coghill ^i point out that, because of this, a 

 given sample of penicillin may display apparently different anti- 

 bacterial properties depending on the test organism used. Pure 

 sodium penicillin G has recently been chosen as the international 

 standard, of which 0.6 ^g. corresponds to one international unit. For 

 further details on penicillin, see Herrell ^^ or Waksman.-* 



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It has been noted that penicillin is primarily active against the 

 Gram-positive group of organisms. Schatz, Bugie, and Waksman -° 



